Signal transduction mechanism by which lipopolysaccharides from various periodontopathic bacteria induce murine B lymphocyte activation

本研究以牙龈卟啉菌（Porphyronwnas gingivalis）、中间普雷沃菌（Prevotella intermedia）、伴放线放线杆菌（Actinobacillus actinomycetemcomitans）和腐蚀艾肯菌（Eikenella corrodens）的脂多糖（LPS）（分别为PgLPS、AaLPS、PiLPS和EiLPS）为材料，探讨了LPS诱导的B淋巴细胞信号转导机制。当使用单克隆抗磷酸酪氨酸抗体在Western印迹分析下检测时，所有LPS以及大肠杆菌LPS（EcLPS）诱导来自LPS应答的C3 H/HeN小鼠的B淋巴细胞中的酪氨酸磷酸化。在LPS低反应的C3 H/HeJ B淋巴细胞中，PgLPS和PiLPS可诱导酪氨酸磷酸化，而AaLPS和EiLPS则不能诱导酪氨酸磷酸化。PgLPS和PiLPS的脂质A部分与EcLPS、AaLPS和EiLPS的脂质A部分有很大不同， ...更多信息 这些结果表明，LPS的脂质A部分可能对LPS诱导的B淋巴细胞酪氨酸磷酸化有促进作用。酪氨酸激酶抑制剂除莠霉素A和Lenistein的治疗，废除了LPS诱导的酪氨酸磷酸化和增殖反应，这表明LPS诱导的酪氨酸磷酸化可能是一个重要的信号事件，可能导致细胞反应。然而，用磷酸酶抑制剂（氧化苯胂）处理没有观察到明显的效果。此外，增加的丝氨酸/苏氨酸蛋白磷酸化在B淋巴细胞中也可能是重要的，因为LPS刺激后的增殖反应被抑制预孵育与丝氨酸/苏氨酸激酶抑制剂，staurosponne。综上所述，本研究结果表明，围栏牙病细菌具有通过脂质A部分诱导B淋巴细胞刺激的有效性质，其中增加的酪氨酸磷酸化以及随后的其他蛋白质磷酸化可能是可能导致细胞应答的重要信号事件。少

In this study using the Iipopolysaccharides (LPS) from Porphyronwnas gingivalis as well as other periodontopathic bacteria including Prevotella intermedia, Actinobacillus actinomycetemcomitans and Eikenella corrodens (PgLPS, AaLPS, PiLPS and EiLPS, respectively), the nature of LPS-induced signal transduction mechanism that mediates later cellular responses of Blymphocytes was examined. When detected under Western blot analysis by using the monoclonal anti-phosphotyrosine antibody, all the LPSs as well as Escherichia coli LPS (EcLPS) induced tyrosine phosphorylation in the B lymphocytes from LPS-responsive C3H/HeN mice. In the LPS-hyporesponsive C3H/HeJ B lymphocytes, however, the trigger signals could be induced by PgLPS and PiLPS, but not by AaLPS or EiLPS.Furtherrnore, lipid A from Salmonella minnesota also induced tyrosine phosphorylation in C3H/HeN B lymphocytes. It was reported that the lipid A moieties of PgLPS and PiLPS were quite different from those of EcLPS, AaLPS or EiLPS.Th … More us, these results si.iggest that lipid A moiety of LPS could be potent for the LPS-induced tyrosine phosphoxylation in B lymphocytes. The treatment with tyrosine kinase inhibitors, herbimycin A and Lenistein, abrogated the LPS-induced tyrosine phosphorylation and the proliferative response, suggesting that LPS-induced tyrosine phosphorylation could be an important signaling event that might lead to cellular responses. However, no obvious effect has been observed by the treatment with a phosphatase inhibitor (phenylarsine oxide). In addition, increased serine threonine protein phosphorylation in B lymphocytes could be also important, since the proliferative response following LPS stimulation was inhibited by the preincubation with a serine threonine kinase inhibitor, staurosponne. Taken together, the present findings suggest that the pen odontopathic bacteria have a potent property to induce the stimulation of B lymphocytes by the lipid A moiety, in which increased tyrosine phosphorylation folJowed by other protein phosphorylations could be important signaling events that might lead to cellular responses. Less